Four Key Risk Factors Drive Dementia Risk Among American Indians, Study Finds

Dementia is one of the most consequential health challenges of an aging global population, yet the strategies proposed to prevent it have largely been built on evidence drawn from predominantly white, urban, and well-resourced cohorts. A new study led by researchers at Boston University Chobanian & Avedisian School of Medicine, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association and supported by the National Institutes of Health, now provides one of the most detailed examinations to date of how dementia risk factors operate in an American Indian population. The findings suggest that the widely cited prevention model derived from global data does not translate cleanly to Indigenous communities, and that prevention efforts must be tailored rather than transplanted.

The research team set out to test a framework that has become a cornerstone of dementia prevention policy worldwide. In prior work, the Lancet Commission identified fourteen modifiable risk factors across the life course that are collectively responsible for up to 45 percent of dementia cases in the general population. These factors span early life, midlife, and later life, and include limited education, hearing loss, elevated low-density lipoprotein cholesterol, depression, a history of traumatic brain injury, physical inactivity, diabetes, smoking, hypertension, obesity, excess alcohol use, social isolation, exposure to air pollution, and vision loss. The 45 percent figure is expressed as a population attributable fraction, a statistical measure representing the proportion of disease in a population that could theoretically be eliminated if a given risk factor were removed.

Population attributable fraction is a powerful tool for public health planning because it weights both the strength of the association between a risk factor and a disease and how common that factor is in the population. A factor that doubles risk but affects only a small fraction of people may contribute less to the overall disease burden than a modest risk elevation that touches nearly everyone. By calculating population attributable fractions for dementia risk factors in American Indian communities, the Boston University researchers could identify which interventions might deliver the greatest benefit in this specific population, rather than relying on estimates derived from very different demographic and socioeconomic contexts.

When the researchers validated the Lancet Commission model among older American Indians, the results diverged sharply from the global pattern. Of the fourteen established factors, ten could be evaluated in the cohort, and only four showed statistically significant associations with vascular and Alzheimer’s dementias: limited education, hypertension, social isolation, and depression. The population attributable fractions for these four factors were striking. Limited education accounted for 19 percent, hypertension for 11 percent, and social isolation for 13 percent of dementia risk in the population. Depression stood out with an attributable fraction of 60 percent, though the researchers cautioned that this figure may be an overestimate, because depression can also be an early symptom of dementia rather than a purely causal factor, a form of reverse causation that complicates interpretation.

Together, these four factors may represent the highest-impact targets for dementia prevention programs designed for Native American populations. The pattern itself is informative. Some of the factors that loom large in global models, such as hearing loss, diabetes, and smoking, did not reach statistical significance in this cohort, while others were more or less prevalent than in the general population. The researchers concluded that American Indian communities may carry a complex and unique constellation of contributing factors that elevate risk of both vascular dementia, which stems from impaired blood flow to the brain, and Alzheimer’s dementia, the most common neurodegenerative form of the disease.

Corresponding author Astrid Suchy-Dicey, PhD, associate professor of medicine at Boston University Chobanian & Avedisian School of Medicine, emphasized that the findings call for careful consideration of exposures and tailored prevention programs across the life course when assessing cognitive risk for Indigenous populations. She noted that later-life factors such as social isolation and depression are likely to provide efficient targets for community interventions, while public health programs designed to improve the treatment and control of hypertension and cardiovascular conditions are critically needed to address persistent health inequities. Structural improvements to educational systems, learning resources, and skills training for rural communities, she added, may result in better life-course trajectories for everyone living in those communities.

The distinction between midlife and later-life interventions carries practical weight. Hypertension is a classic midlife target: elevated blood pressure damages the small vessels of the brain over decades, contributing to both stroke-related vascular injury and the accumulation of Alzheimer’s pathology. Controlling it requires sustained clinical infrastructure, medication access, and cardiovascular care, resources that have historically been unevenly distributed in rural and Tribal communities. Social isolation and depression, by contrast, are potentially more amenable to community-level programs that strengthen social connection, mental health support, and cultural engagement, interventions that can be designed and delivered within the communities themselves.

The researchers also observed that because of the high burden of some risk factors, this population may develop neurodegenerative and vascular brain injury earlier in life, or progress toward dementia more rapidly once injury begins. This possibility has implications for how future studies are designed. Suchy-Dicey noted that future research should evaluate risk in younger groups, perhaps as young as 35 to 45 years of age, in order to observe the conversion from healthy cognition to symptomatic disease and to evaluate risk with lower potential for bias due to selective survival. Selective survival is a well-known problem in aging research: individuals with the heaviest burden of risk factors may die before they can be enrolled in studies of older adults, making surviving cohorts appear healthier than the population truly was and understating the true contribution of those risks.

The evidence base for the new analysis comes from the Strong Heart Study, a large cohort of American Indians aged 45 to 95 years residing in Tribal communities in the U.S. Southwest, Southern Plains, and Northern Plains. Participants attended multiple examination visits from midlife into late life and underwent cognitive assessment, allowing the researchers to track changes over time. Using regression models, the team estimated the prevalence of each risk factor, the relative risk of dementia associated with each, and the population attributable fraction for the cohort. This longitudinal design, spanning decades of adult life, is essential for distinguishing factors that precede cognitive decline from those that merely accompany it.

Equally notable is how the research was conducted. Strong Heart Study research is carried out in collaboration with the participating Tribal communities under a community-participatory research model, which centers research participants and Tribes throughout the research process, from study design through interpretation and dissemination. This approach stands in contrast to a long history of extractive research practices in Indigenous communities and reflects a growing recognition that trustworthy science requires genuine partnership. The authors argue that their findings underscore the importance of including many groups in population research, because models built on one population can mislead when applied to another. For the most valid understanding of health and disease in all peoples, dementia prevention science must reflect the diversity of the populations it aims to serve, and the four factors identified here, limited education, hypertension, social isolation, and depression, offer a starting point for prevention strategies built by and for American Indian communities.

Subject of Research: Modifiable dementia risk factors and population attributable fractions in American Indian populations

Article Title: BU researchers identify risk factors for dementia among American Indians

Article References: BU researchers identify risk factors for dementia among American Indians. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: dementia, American Indians, Alzheimer's disease, vascular dementia, population attributable fraction, hypertension, social isolation, depression, education, Strong Heart Study, Boston University, public health